Radiometals produced by liquid targets for molecular imaging of cancer

新的乳腺癌药物越来越多地针对参与癌症进展的特定蛋白，例如表皮生长因子受体(HER2)。这些新药通常只对一小部分患者有利，医疗保健系统的成本非常高(针对HER2的赫赛汀的每位患者每年超过4万美元)。在选择这些昂贵的治疗方法之前，医生需要了解患者的肿瘤中是否存在药物靶点。预测蛋白的存在，也被称为生物标记物，可以通过使用特殊的实验室技术进行肿瘤活检来确定。然而，对已经扩散的肿瘤进行活检通常是不可能的，而且不同肿瘤部位的生物标记物含量可能不同。分子成像技术，如正电子发射断层扫描结合计算机断层扫描(PET/CT)，可以使用极低浓度的放射性探针，成为检测生物标记物的一种强大的非侵入性工具。该项目的目的是开发用于PET/CT成像的新的放射性同位素生产技术。利用这些放射性同位素，该项目将开发新的显像剂，使医生能够找出患者是否表达与目前用于治疗HER2阳性乳腺癌的药物耐药有关的HER2变体。令人感兴趣的放射性同位素被称为锆-89、镓-68、钇-86和钪-44。其中许多放射性同位素目前在加拿大无法获得。制造它们的传统方法涉及使用回旋加速器照射的固体靶，但这种方法需要特殊的设备和专业知识，这是大多数设施所不具备的。我们的多学科专家团队将与我们的合作者和工业合作伙伴一起，对放射性同位素的产量进行理论模拟，设计新的盐溶液靶标来制造放射性同位素，优化这些放射性同位素的生产条件，开发分离和提纯的方法，并将这些同位素连接到

New breast cancer drugs are increasingly targeted to specific proteins involved in cancer progression, such as the epidermal growth factor receptor (HER2). These new drugs typically benefit only a small proportion of patients, at very high cost to the health care system (over $40,000 per patient per year for Herceptin, which targets HER2). Physicians need information about whether a drug target is present in patients' tumours before selecting these expensive treatments. The presence of a predictive protein, also called a biomarker, can be determined by taking a tumour biopsy using special laboratory techniques. However, it is often impossible to biopsy tumours that have spread, and biomarker content may vary from one tumour site to another. Molecular imaging technologies such as positron emission tomography combined with computed tomography (PET/CT) can be a powerful, non invasive tool to detect biomarkers, using extremely low concentrations of radioactive probes. The purpose of this project is to develop novel radioisotope production technologies used for PET/CT imaging. With these radioisotopes, the project will develop new imaging agents that will allow physicians to find out if patients express a variant of HER2 that is associated with resistance to the current drug used to treat HER2 positive breast cancers. The radioisotopes of interest are called zirconium-89, gallium-68, yttrium-86 and scandium-44. Many of these radioisotopes are currently unavailable in Canada. The traditional production methods to make them involve the use of solid targets, which are irradiated by a cyclotron, but this approach requires specific equipment and expertise unavailable in most facilities. Our multidisciplinary team of experts, along with our collaborators and industrial partner, will conduct theoretical simulation of radioisotope production yields, design new salt-solution targets to make the radioisotopes, optimize the production conditions of these radioisotopes, develop methods to separate and purify them, and attach the isotopes to